Abstract

Background

Insulin-like growth factor-I (IGF-I) exerts neuroprotective actions in the central
nervous system that are mediated at least in part by control of activation of astrocytes.
In this study we have assessed the efficacy of exogenous IGF-I and IGF-I gene therapy
in reducing the inflammatory response of astrocytes from cerebral cortex.

Methods

An adenoviral vector harboring the rat IGF-I gene and a control adenoviral vector
harboring a hybrid gene encoding the herpes simplex virus type 1 thymidine kinase
fused to Aequorea victoria enhanced green fluorescent protein were used in this study. Primary astrocytes from
mice cerebral cortex were incubated for 24 h or 72 h with vehicle, IGF-I, the IGF-I
adenoviral vector, or control vector; and exposed to bacterial lipopolysaccharide
to induce an inflammatory response. IGF-I levels were measured by radioimmunoassay.
Levels of interleukin 6, tumor necrosis factor-α, interleukin-1β and toll-like receptor
4 mRNA were assessed by quantitative real-time polymerase chain reaction. Levels of
IGF-I receptor and IGF binding proteins 2 and 3 were assessed by western blotting.
The subcellular distribution of nuclear factor κB (p65) was assessed by immunocytochemistry.
Statistical significance was assessed by one way analysis of variance followed by
the Bonferroni pot hoc test.

Conclusion

These findings demonstrate efficacy of exogenous IGF-I and of IGF-I gene therapy in
reducing the inflammatory response of astrocytes. IGF-I gene therapy may represent
a new approach to reduce inflammatory reactions in glial cells.